RNA damages and RNA quality control

RNA损伤和RNA质量控制

• 批准号: 20570168
• 负责人: HAYAKAWA Hiroshi
• 金额: $ 3.16万
• 依托单位: Fukuoka Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20570168/
• 关键词: RNA; 酸化ストレス; DNA修復; 品質管理; 核酸損傷; DNA修復・損傷; 質量分析; RNA品質管理; RNA結合蛋白; 異常タンパク; 品質管理機構; 突然変異; 酸化損傷

We searched for proteins that specifically bind to 8-oxoguanine-containing RNA from human HeLa cell extracts, and the candidate proteins were identified using mass spectrometry. Among the identified candidates, splicing isoform 1 of heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) and splicing isoform C1 of heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) exhibited strong abilities to bind to oxidized RNA. The amount of HNRNPD protein rapidly decreased when cells were exposed to hydrogen peroxide, an agent that enhances oxidative stress. Moreover, the suppression of HNRNPD expression by siRNA caused cells to exhibit an increased sensitivity to hydrogen peroxide. The application of siRNA against HNRNPC also caused an increase in sensitivity to hydrogen peroxide. Since no additive effect was observed with a combined addition of siRNAs for HNRNPD and HNRNPC, we concluded that the two proteins may function in the same mechanism for the accurate gene expression.

我们搜索了从人HeLa细胞提取物中特异性结合的蛋白质，并使用质谱法鉴定了候选蛋白。在已确定的候选物中，异质核核糖核蛋白D0（HNRNPD）和异质核核糖核蛋白C1/C2（HNRNPC）的剪接同工型1和剪接同工型C1表现出强大的能力，表现出强大的能力与氧化RNA结合。当细胞暴露于过氧化氢时，HNRNPD蛋白的量会迅速降低，这种药物会增强氧化应激。此外，siRNA对HNRNPD表达的抑制导致细胞对过氧化氢的敏感性增加。 siRNA对HNRNPC的应用也导致对过氧化氢的敏感性增加。由于未观察到HNRNPD和HNRNPC的siRNA共同添加siRNA，因此我们得出结论，这两种蛋白质可能在相同的机制中起作用，以实现准确的基因表达。

项目成果

Mammalian proteins for eliminating oxidized forms of RNA and its precursors for accurate protein synthesis

哺乳动物蛋白质，用于消除氧化形式的 RNA 及其前体，以实现准确的蛋白质合成

• 发表时间: 2009
• 作者: Hiroshi Hayakawa;Riyoko Ito;Mutsuo Sekiguchi
• 通讯作者: Mutsuo Sekiguchi

酸化されたRNAやRNA前駆体を生体から排除し、正確な遺伝情報伝達を保証するヒトのタンパク質群

一组人类蛋白质，可消除体内氧化的 RNA 和 RNA 前体，并确保遗传信息的准确传递。

• 发表时间: 2009
• 作者: 早川浩;伊東理世子;関口睦夫
• 通讯作者: 関口睦夫

Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress

• DOI: 10.1016/j.bbrc.2010.11.011
• 发表时间: 2010-12-10
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Hayakawa, Hiroshi;Fujikane, Aya;Sekiguchi, Mutsuo
• 通讯作者: Sekiguchi, Mutsuo